Molecular diagnosis of the fragile X and FRAXE syndromes in patients with mental retardation of unknown cause in Mexico

The fragile X syndrome (Fra-X) is the most common cause of inherited mental retardation with X-linked semi-dominant inheritance. The prevalence of Fra -X in the Mexican population is unknown. The aim of this population screeni ng study was to determine if Fra-X or FRAXE mutations are the cause of a nu mber of cases of mental retardation in a sample of Mexican children with me ntal retardation of unknown cause (MRUC) and to stress the importance of pe rforming molecular analysis of the FMR-I gene in all patients with MRUC. We report here the direct analysis of CGG and GCC repeats within the FMR-1 an d FMR-2 genes, respectively, in 62 unrelated patients with MRUC. Two male i ndex cases had the CGG expansion, although they did not express the Xq27.3 fragile site cytogenetically. Fra-X diagnosis was highly suspected on a cli nical basis in one of the patients, but not in the other. Both mothers were found to be premutation carriers. The molecular studies of FMR-1 showed th at the proportion of MRUC patients with Fra-X is 3.2 %. This frequency was not significantly different to that reported in most populations. As report ed in other series, no patients with FRAXE were found in our sample. Our fi ndings confirm that the molecular analysis of the FMR-I gene is necessary i n MRUC patients to achieve unequivocal diagnosis of fragile X syndrome, car rier premutation detection and for accurate genetic counseling. (C) 2000 Ed itions scientifiques et medicales Elsevier SAS.